The epidemiology of drug-related hospital admissions in paediatrics – a systematic review

Background: Despite previous efforts, medication safety in paediatrics remains a major concern. To inform improvement strategies and further research especially in outpatient care, we systematically reviewed the literature on the frequency and nature of drug-related hospital admissions in children. Methods: Searches covered Embase, Medline, Web of Science, grey literature sources and relevant article citations. Studies reporting epidemiological data on paediatric drug-related hospital admissions published between 01/2000 and 01/2024 were eligible. Study identification, data extraction, and critical appraisal were conducted independently in duplicate using templates based on the ’Joanna Briggs Institute’ recommendations. Results: The review included data from 45 studies reporting > 24,000 hospitalisations for adverse drug events (ADEs) or adverse drug reactions (ADRs). Due to different reference groups, a total of 52 relative frequency values were provided. We stratified these results by study characteristics. As a percentage of inpatients, the highest frequency of drug-related hospitalisation was found with ‘intensive ADE monitoring’, ranging from 3.1% to 5.8% (5 values), whereas with ‘routine ADE monitoring’, it ranged from 0.2% to 1.0% (3 values). The relative frequencies of ‘ADR-related hospitalisations’ ranged from 0.2% to 6.9% for ‘intensive monitoring’ (23 values) and from 0.04% to 3.8% for ‘routine monitoring’ (8 values). Per emergency department visits, five relative frequency values ranged from 0.1% to 3.8% in studies with ‘intensive ADE monitoring’, while all other eight values were ≤ 0.1%. Heterogeneity prevented pooled estimates. Studies rarely reported on the nature of the problems, or studies with broader objectives lacked disaggregated data. Limited data indicated that one in three (median) drug-related admissions could have been prevented, especially by more attentive prescribing. Besides polypharmacy and oncological therapy, no other risk factors could be clearly identified. Insufficient information and a high risk of bias, especially in retrospective and routine observational studies, hampered the assessment. Conclusion: Given the high frequency of drug-related hospitalisations, medication safety in paediatrics needs to be further improved. As routine identification appears unreliable, clinical awareness needs to be raised. To gain more profound insights especially for generating improvement strategies, we have to address under-reporting and methodological issues in future research

Erratum: Zahn et al. Manipulation of Medicinal Products for Oral Administration to Paediatric Patients at a German University Hospital: An Observational Study. Pharmaceutics 2020, 12, 583

The authors wish to make the following corrections to the affiliation and acknowledgments part [...

Metamizole Use in Children: Analysis of Drug Utilisation and Adverse Drug Reactions at a German University Hospital between 2015 and 2020

Background Metamizole use is controversially discussed due to its potentially serious adverse drug reactions (ADRs). In Germany, however, it remains a popular analgesic and antipyretic drug. Objective The aim of this study was to discuss the safety profile of metamizole in children by analysing the inpatient prescription patterns and presenting the metamizole-related ADRs at a paediatric hospital between 2015 and 2020. Methods Metamizole utilisation data were retrospectively analysed from electronic medical records. ADRs were prospectively recorded via the hospital’s stimulated reporting system and analysed accordingly. Patients aged < 18 years admitted to one of the general wards of the department of paediatrics and adolescent medicine of a German university hospital between June 2015 and May 2020 who received at least one drug therapy within their inpatient stay were included in the analysis. Causality of ADRs was rated according to the World Health Organisation causality assessment. Results In 31.7% (3759/11,857) of the inpatient stays of 7809 patients, metamizole was administered. Metamizole exposure was highest in adolescents (37.9%) and lowest in newborns (9.9%). Overall, metamizole was administered parenterally in about 90%. Three cases of agranulocytosis, one allergic shock and one rash with possible or higher causality to metamizole treatment were reported. Three of these occurred prior to hospitalisation. All patients recovered without remaining harm. Discussion Metamizole is commonly used in paediatric inpatients in Germany. Serious ADRs occur but rarely. Continuous monitoring of drug therapy through, for example, stimulated reporting systems ensures that serious ADRs are detected, and appropriate interventions can be introduced

Development and Evaluation of a Web-Based Paediatric Drug Information System for Germany

Background: Off-label use is frequent in paediatrics but that does not necessarily mean that the risk-benefit ratio is negative. Nevertheless, evidence-based data is essential for safe drug therapy. In Germany, there is no publicly available compendium providing transparent, evidence-based information for paediatric pharmacotherapy to date. This work describes the development of a web-based paediatric drug information system (PDIS) for Germany and its evaluation by health care professionals (HCP). Methods: Since 2012, a PDIS is being developed by the authors and is supported by the Federal Ministry of Health since 2016. Dosing recommendations were established based on systematic literature reviews and subsequent evaluation by clinical experts. The prototype was evaluated by HCP. Based on the results, the further development was concluded. Results: 92% of HCP believed that the PDIS could improve the quality of prescribing, as currently available information is deficient. Besides the license and formulations, dosing recommendations were the most relevant modules. A dosage calculator was the most wanted improvement. To facilitate sustainability of future development, a collaboration with the Dutch Kinderformularium was established. As of 2021, the database will be available to German HCP. Conclusion: The fundamentals for a German PDIS were established, and vital steps were taken towards successful continuation

Removal of hydrogen from Ti VT 1-0 under action of accelerated electrons

The process of hydrogen removal from titanium of VT1-0 grade under the action of accelerated electrons has been studied experimentally. The irradiation was carried out by an electron beam with energies of 25-40 keV during 15-60 min. The information on the hydrogen content in samples from titanium of VT1-0 grade has been obtained both before and after irradiation with accelerated electrons. The activation energy of hydrogen desorption from titanium has been calculated. It was found that the increase of the time and the energy of an irradiation lead to the decrease of the residual hydrogen content in the titanium samples

Routine Surveillance of SARS-CoV-2 Serostatus in Pediatrics Allows Monitoring of Humoral Response

The occurrence of SARS-CoV-2 infections during the pandemic was mainly based on PCR testing of symptomatic patients. However, with new variants, vaccinations, and the changing of the clinical disease severity, knowledge about general immunity is elusive. For public health systems, timely knowledge of these conditions is essential, but it is particularly scarce for the pediatric population. Therefore, in this study, we wanted to investigate the spike and nucleocapsid seroprevalence in pediatric patients using routine residual blood tests collected during the pandemic. This prospective observational study was conducted over seven one-month periods. Herein, the latest four time periods (November 2021, January 2022, March 2022, and May 2022) are depicted. Each patient of a tertiary-care center in Germany was anonymized after collection of clinical diagnosis (ICD-10) and then routinely tested for the respective spike and nucleocapsid SARS-CoV-2 antibody titer. A total of 3235 blood samples from four time periods were included. Spike seroprevalence rose from 37.6% to 51.9% to 70.5% to 85.1% and nucleocapsid seroprevalence from 11.6% to 17.0% to 36.7% to 58.1% in May 2022. In detail, significant changes in seroprevalence between age groups but not between sex or diagnosis groups were found. Quantitative measures revealed rising spike and constant nucleocapsid antibody levels over the pandemic with a half-life of 102 days for spike and 45 days for nucleocapsid antibodies. Routine laboratory assessment of SARS-CoV-2 in residual blood specimens of pediatric hospitals enables monitoring of the seroprevalence and may allow inferences about general immunity in this cohort.</jats:p

Surveillance of acute SARS-CoV-2 infections in elementary schools and daycare facilities in Bavaria, Germany (09/2020–03/2021)

Introduction: Here we report our results of a multi-center, open cohort study ("COVID-Kids-Bavaria") investigating the distribution of acute SARS-CoV-2 infections among children and staff in 99 daycare facilities and 48 elementary schools in Bavaria, Germany. Materials and Methods: Overall, 2,568 children (1,337 school children, 1,231 preschool children) and 1,288 adults (466 teachers, 822 daycare staff) consented to participate in the study and were randomly tested in three consecutive phases (September/October 2020, November/December 2020, March 2021). In total, 7,062 throat swabs were analyzed for SARS-CoV-2 by commercial RT-PCR kits. Results: In phase I, only one daycare worker tested positive. In phase II, SARS-CoV-2 was detected in three daycare workers, two preschool children, and seven school children. In phase III, no sample tested positive. This corresponds to a positive test rate of 0.05% in phase I, 0.4% in phase II and 0% in phase III. Correlation of a positive PCR test result with the local-7-day incidence values showed a strong association of a 7-day-incidence of more than 100/100,000 as compared to &lt;100/100,000 (OR = 10.3 [1.5-438], p &lt; 0.005). After phase III, antibody testing was offered to 713 study participants in elementary schools. A seroprevalence rate of 7.7% (students) and 4.5% (teachers) was determined. Discussion: During the initial waves of the SARS-CoV-2 pandemic, the risk of a positive SARS-CoV-2 result correlated positively with the local 7-day incidence. Hence, the occurrence of SARS-CoV-2 infections were reflected in schools and daycare facilities. An increased risk of SARS-CoV-2 transmission in the setting of daycare and elementary schooling was unlikely

Phagosomal signalling of the C-type lectin receptor Dectin-1 is terminated by intramembrane proteolysis

Dectin-1 is a critical component of the innate sensing repertoire which is involved in pattern based recognition of fungal pathogens. Here the authors show that intramembrane proteolysis is involved in the regulation of the antifungal host response by termination of the phagosomal signalling of Dectin-1. Sensing of pathogens by pattern recognition receptors (PRR) is critical to initiate protective host defence reactions. However, activation of the immune system has to be carefully titrated to avoid tissue damage necessitating mechanisms to control and terminate PRR signalling. Dectin-1 is a PRR for fungal beta-glucans on immune cells that is rapidly internalised after ligand-binding. Here, we demonstrate that pathogen recognition by the Dectin-1a isoform results in the formation of a stable receptor fragment devoid of the ligand binding domain. This fragment persists in phagosomal membranes and contributes to signal transduction which is terminated by the intramembrane proteases Signal Peptide Peptidase-like (SPPL) 2a and 2b. Consequently, immune cells lacking SPPL2b demonstrate increased anti-fungal ROS production, killing capacity and cytokine responses. The identified mechanism allows to uncouple the PRR signalling response from delivery of the pathogen to degradative compartments and identifies intramembrane proteases as part of a regulatory circuit to control anti-fungal immune responses